Abstract
It has been proposed that endothelial progenitor cells (EPC), originating from the bone marrow contribute to neo-angiogenesis in vivo by forming endothelial cells. Once released in the bloodstream, EPC home at the site of vascular damage where they participate in endothelium regeneration. In this process CXCR4 plays a key role. Recently we demonstrated that a prolonged therapy with phosphodiesterase-5 (PDE5) inhibitors does improve endothelial function and increases circulating EPC, suggesting a role of PDE5 in EPC physiology. Here we tested the expression of PDE5 and CXCR4 on cultured, circulating, and bone marrow resident EPC, and we studied the effect in vivo and in vitro of PDE5 inhibition after administration of a PDE5 inhibitor (tadalafil) on EPC, in term of CXCR4 expression. We documented that in vivo and in vitro EPC express both PDE5 and CXCR4, and that tadalafil administration induced a significant increase in EPC number and the relative CXCR4 expression. This effect is inhibited by selective CXCR4 antagonist. We thus demonstrated that PDE5 inhibition acts on CXCR4 signalling in EPC and we can suppose an involvement of cGMP second messenger system in both EPC release from the bone marrow and EPC-mediated peripheral re-endothelization.
Keywords: Endothelial progenitor cells, angiogenesis, PDE5, CXCR4, tadalafil, cGMP
Current Drug Delivery
Title: Phosphodiesterase-5 Inhibitor Tadalafil Acts on Endothelial Progenitor Cells by CXCR4 Signalling
Volume: 7 Issue: 4
Author(s): Carlo Foresta, Luca De Toni, Sabina Magagna, Alessandro Galan and Andrea Garolla
Affiliation:
Keywords: Endothelial progenitor cells, angiogenesis, PDE5, CXCR4, tadalafil, cGMP
Abstract: It has been proposed that endothelial progenitor cells (EPC), originating from the bone marrow contribute to neo-angiogenesis in vivo by forming endothelial cells. Once released in the bloodstream, EPC home at the site of vascular damage where they participate in endothelium regeneration. In this process CXCR4 plays a key role. Recently we demonstrated that a prolonged therapy with phosphodiesterase-5 (PDE5) inhibitors does improve endothelial function and increases circulating EPC, suggesting a role of PDE5 in EPC physiology. Here we tested the expression of PDE5 and CXCR4 on cultured, circulating, and bone marrow resident EPC, and we studied the effect in vivo and in vitro of PDE5 inhibition after administration of a PDE5 inhibitor (tadalafil) on EPC, in term of CXCR4 expression. We documented that in vivo and in vitro EPC express both PDE5 and CXCR4, and that tadalafil administration induced a significant increase in EPC number and the relative CXCR4 expression. This effect is inhibited by selective CXCR4 antagonist. We thus demonstrated that PDE5 inhibition acts on CXCR4 signalling in EPC and we can suppose an involvement of cGMP second messenger system in both EPC release from the bone marrow and EPC-mediated peripheral re-endothelization.
Export Options
About this article
Cite this article as:
Foresta Carlo, De Toni Luca, Magagna Sabina, Galan Alessandro and Garolla Andrea, Phosphodiesterase-5 Inhibitor Tadalafil Acts on Endothelial Progenitor Cells by CXCR4 Signalling, Current Drug Delivery 2010; 7 (4) . https://dx.doi.org/10.2174/156720110793360595
DOI https://dx.doi.org/10.2174/156720110793360595 |
Print ISSN 1567-2018 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5704 |
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Vitamin, Mineral, and Drug Absorption Following Bariatric Surgery
Current Drug Metabolism Overview of Hyperuricaemia and Gout
Current Pharmaceutical Design Extended-spectrum Beta-lactamase Production in Pseudomonas aeruginosa and Acinetobacter baumannii Strains: Epidemiology, Molecular Characterization and Novel Proteomics-based Diagnostic Tools
Current Proteomics Human Islet Transplantation: Current Status and Future Direction
Micro and Nanosystems Anti-inflammatory and Immune Therapy for Alzheimers Disease: Current Status and Future Directions
Current Neuropharmacology Role of Nanoparticles in Drug Delivery and Regenerative Therapy for Bone Diseases
Current Drug Delivery Development of Ribonucleotide Reductase Inhibitors: A Review on Structure Activity Relationships
Mini-Reviews in Medicinal Chemistry In Patients with HIV-Infection, Chromium Supplementation Improves Insulin Resistance and Other Metabolic Abnormalities: A Randomized, Double-Blind, Placebo Controlled Trial
Current HIV Research Antioxidants in Health, Disease and Aging
CNS & Neurological Disorders - Drug Targets New Therapies for Sepsis
Current Topics in Medicinal Chemistry Identification of Bioactive Natural Products by Pharmacophore-Based Virtual Screening
Current Pharmaceutical Design Covid-19 in Man: A Very Dangerous Affair
Endocrine, Metabolic & Immune Disorders - Drug Targets Review Metabolomics: A New Approach to Drug Delivery in Perinatology
Current Medicinal Chemistry Inhibition of Histone Deacetylases: A Pharmacological Approach to the Treatment of Non-Cancer Disorders
Current Topics in Medicinal Chemistry Biomarker Diversity, Validation and Clinical Translation: Tenets for Emergent Personalized Medicine Initiatives
Current Pharmacogenomics and Personalized Medicine Interactions between Transporters and Herbal Medicines/Drugs: A Focus on Hepatoprotective Compounds
Current Drug Metabolism The Promise of Plant Polyphenols as the Golden Standard Skin Anti-Inflammatory Agents
Current Drug Metabolism Comprehensive Analysis of SARS-COV-2 Drug Targets and Pharmacological Aspects in Treating the COVID-19
Current Molecular Pharmacology Current Trends and Future Strategies for the Global Impact of COVID-19 Pandemic
Coronaviruses Comprehensive Account on the Synthesis of (-)-Balanol and its Analogues
Current Organic Synthesis